Signet-Ring Cell Squamous Cell Carcinoma: A Biphenotypic Neoplasm of the Gastro-Esophageal Junction with Uncertain Biological Potential: Case Report and Literature Review.

The signet-ring cell variant of squamous cell carcinoma (SCC) is an extremely rare histological subtype, with only 24 cases (including the present case) reported in the Medline database: 15 affecting the external surface of the body, 3 in the lung, 2 affecting the uterine cervix, 1 involving the gingiva, another one affecting the esophagus and the present case that is the first reported at the gastro-esophageal junction (GEJ). In one case, the location of the lesion was not mentioned. A 59-year-old male patient underwent segmental eso-gastrectomy for carcinoma of the GEJ. The microscopic examination showed a pT3N1-staged SCC composed of solid nests admixed in over 30% of the tumor, with cells having eccentrically located nuclei and clear vacuolated cytoplasm. The signet-ring cells did not show mucinous secretion and were positive for keratin 5/6 and vimentin, with nuclear expression of ß-catenin and Sox2 and focal membrane positivity for E-cadherin. Based on these features, the case was considered a signet-ring SCC with epithelial-mesenchymal transition. Thirty-one months after surgery, the patient was disease-free, with no local recurrence and no known distant metastases. In SCC, a signet-ring cell component might be an indicator of the dedifferentiation of tumor cells towards a mesenchymal molecular subtype.

V-set and immunoglobulin domain containing 1 (VSIG1) as an emerging target for epithelial-mesenchymal transition of gastric cancer.

V-set and Immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule which role in the genesis and evolution of gastric cancer (GC) is not understood. Only three Medline-indexed papers have focused on the role of VSIG1 in GC. The clinicopathological features of 94 GCs were examined in association with immunohistochemical (IHC) patterns of VSIG1, E-cadherin, and ß-catenin which were assessed in the tumor core (central) vs. invasive edge. Cases were classified depending on the VSIG1 expression: membrane/membrane in both core and invasive front; null/negative staining in both core and invasive front; and cases with translocational patterns: membrane core/cytoplasmic buds and cytoplasmic core/null buds. Most of the tumors showed null pattern (n = 54). Cases with translocational patterns (n = 20) were GCs with a high lymph node ratio value (≥ 0.26) and advanced Dukes-MAC-like stage. Of the 20 total cases, 9 showed membrane-to-nuclear translocation of ß-catenin and loss of E-cadherin, as indicators of epithelial-mesenchymal transition. All cases with membrane/membrane pattern (n = 20) involved the distal stomach. The poorest overall survival was registered in patients with subcellular translocation of VSIG1, compared to those with either membrane/membrane or null patterns (p = 0.002). In GC, VSIG1 acts as an adhesion membrane protein but its membrane-cytoplasmic translocation can be an indicator of epithelial-mesenchymal transition due to cytoplasmic VSIG1-mediated activation of canonical Wnt/ß-catenin signaling pathway.

In-House Validated Map of Lymph Node Stations in a Prospective Cohort of Colorectal Cancer: A Tool for a Better Preoperative Staging.

Preoperative staging of colorectal cancer (CRC) based on imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is crucial for identification and then removal of the positive lymph nodes (LNs). The aim of this study was to evaluate the correlation between preoperatively seen morphologic criteria (number, size, shape, structure, borders, or enhancement patterns) and histopathological features of LNs using an in-house validated map of nodal stations. A total of 112 patients with CRC that underwent surgery were preoperatively evaluated by CT scans. The locoregional, intermediate, and central LNs were CT-mapped and then removed during open laparotomy and examined under microscope. The analysis of correlations was interpreted using the suspicious-to-positive ratio (SPR) parameter. The greatest correlation was found in tumors located in the sigmoid colon, descending colon and middle rectum; SPR value was 1.12, 1.18, and 1.26, respectively. SPR proved to be 0.59 for cases of the transverse colon. Regarding the enhancement type, the dotted pattern was mostly correlated with metastatic LNs (OR: 7.84; p < 0.0001), while the homogenous pattern proved a reliable indicator of nonmetastatic LNs (OR: 1.99; p < 0.05). A total of 1809 LNs were harvested, with a median value of 15 ± 1.34 LNs/case. Transdisciplinary approach of CRC focused on pre-, intra-, and postoperatively mapping of LNs might increase the accuracy of detecting metastasized nodes for tumors of the distal colon and middle rectum but not for those of the transverse colon. In addition to morphologic criteria, the enhancement pattern of LNs can be used as a predictor of nodal involvement improving the CT-based preoperative staging.

Chylous Ascites, Unusual Association with Ductal Pancreatic Adenocarcinoma with Plasmacytoid Morphology: A Case Report and Literature Review.

Chylous ascites represents a relatively uncommon condition. In this paper, we present a case of chyloperitoneum associated with pancreatic ductal adenocarcinoma (PDAC) and a review of literature regarding chylous ascites. A 76-year-old male patient was admitted in emergency department with acute abdomen. A pancreatic cancer was suspected. Subtotal spleno-pancreatectomy, for a nodular mass infiltrating the mild and distal portion of the pancreas, was necessary. During surgical intervention in the peritoneal cavity, a moderate quantity of whitish and thick consistency fluid with milk-like appearance was observed to be accumulated. After examination of the fluid, chyloperitoneum was diagnosed. The histologic examination showed a PDAC, with multiple emboli in lymph vessels, with tumor cells with plasmacytoid morphology, diagnosed as lymphangiosis carcinomatosa. The patient died at 3 weeks after surgical intervention. In patients with pancreatic cancer and chylous ascites, suspicion of tumor-related blockage of the lymphatic flow should be suspected. Prognosis of PDAC should be evaluated not only based on the number of lymph node metastases, but also considering the number of lymph vessels with tumor emboli and the architecture of tumor cells. This is the first reported case of a PDAC with plasmacytoid morphology of lymphangiosis carcinomatosa.

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity-The Main Keys for Optimal Approach.

BACKGROUND: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. METHODS: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers ß-catenin and E-cadherin, same as KRAS and BRAF mutations. RESULTS: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. CONCLUSIONS: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors.

HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies.

BACKGROUND: Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. The aim of this study was to examine the expression of c-erbB-2 oncoprotein (HER2), in GC samples, using two commercial immunohistochemical (IHC) antibodies, and to validate the results by checking HER2 gene amplification by fluorescence in situ hybridization (FISH). METHODS: We assessed the IHC expression of HER2 using the polyclonal antibody from Dako and CB11 clone from Leica, in 93 consecutive cases of GC samples. In all of the cases, FISH analysis was also performed using the BOND-MAX platform. RESULTS: No significant difference was observed between the two HER2 antibodies. Of the 93 cases, 22.58% demonstrated at least focal and 1+ HER2 positivity. Seven cases (7.53%) exhibited 3+ expression, and another 7 carcinomas (7.53%) were equivocal (2+). HER2 amplification was seen in 11 cases (11.83%), 10 of which were differentiated adenocarcinomas. In 5 of the cases, 2-5 sections were examined, which proved the extremely high intratumorally/intraglandular heterogeneity. FISH heterogeneity was higher in cases with only 2+ positivity on IHC assessment, compared with those showing at least one small focus of 3+ overexpression. HER2 amplification proved to be an independent negative prognostic factor. CONCLUSIONS: Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method.

Prognostic Impact of the Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratio, in Patients with Rectal Cancer: A Retrospective Study of 1052 Patients.

Despite the description of several new prognostic markers, colorectal cancer still represents the third most frequent cause of cancer-related death. As immunotherapy is considered a therapeutic alternative in such patients, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratio (LMR) are hypothesized to provide reliable prognostic information. A retrospective study was conducted on 1052 patients operated on during 2013-2019 in two clinical hospitals from Hungary and Romania. Inclusion criteria targeted patients over 18 years old, diagnosed with rectal cancer, with preoperatively defined NLR and LMR. The overall survival rate, along with clinical and histopathological data, was evaluated. Overall survival was significantly associated with increased NLR (p = 0.03) and decreased LMR (p = 0.04), with cut-off values of 3.11 and 3.39, respectively. The two parameters were inversely correlated (p < 0.0001). There was no statistically significant association between tumor stage and NLR or LMR (p = 0.30, p = 0.06, respectively). The total mesorectal excision was especially obtained in cases with low NLR (p = 0.0005) and high LMR (p = 0.0009) values. A significant association was also seen between preoperative chemoradiotherapy and high NLR (p = 0.0001) and low LMR (p = 0.0001). In patients with rectal cancer, the preoperative values of NLR and LMR can be used as independent prognostic parameters. An NLR value of ≥3.11 can be used to indicate the response to preoperative chemoradiotherapy, but a low chance of sphincter preservation or obtaining a complete TME. Higher values of NLR and lower values of LMR require a more attentive preoperative evaluation of the mesorectum.

Primary rhabdomyosarcoma: An extremely rare and aggressive variant of male breast cancer.

BACKGROUND: Rhabdomyosarcoma (RMS) of the breast, a mesenchymal neoplasm with skeletal muscle differentiation, is an extremely rare tumour in males, with less than 30 cases published in English-language literature. We report on the first case of a male breast RMS, with an unusual ectomesenchymal/neuroectodermal component. CASE SUMMARY: A 55-year-old, previously healthy male, underwent a radical left mastectomy for an ulcerated tumour mass, occupying the breast and left anterior thoracic wall. The biopsy specimen indicated the presence of a tumour with neural origins, namely a peripheral neuroectodermal tumour (PNET). The surgical specimens identified two components. The rhabdomyosarcomatous component (over 70%) was represented by large pleomorphic cells with positivity for desmin, sarcomeric actin and myogenin. The PNET-like ectomesenchymal component, which was admixed with the RMS cells, and was also revealed during the preoperative biopsy, consisted of small cells which expressed neurofilament, neuron specific enolase and CD99. The microscopic examination, along with the immunohistochemical profile, allowed the diagnosis of an RMS, with unusual ectomesenchymal differentiation. The patient refused the postoperative oncologic therapy and died three months after surgery. CONCLUSION: In patients with RMS of the breast, the PNET-like ectomesenchymal component increases the diagnosis difficulty, especially in biopsy specimens. This differentiation can be immunohistochemically proven and might highlight the possible development of high-grade sarcoma of the breast from remnants of the embryological ectodermal layer.

Cystic low-grade collecting duct renal carcinoma with liver compression - A challenging diagnosis and therapy: A case report.

BACKGROUND: A collecting duct carcinoma is a very rare, malignant renal epithelial tumor. Distant metastases are present in one third of cases at the time of diagnosis. It is known to have a poor prognosis. CASE SUMMARY: A 42-year-old male was sent to our surgery clinic for removal of a 119.2 mm × 108.3 mm encapsulated cystic mass, which was localized in the 8th segment of the right liver lobe. The lesion was first identified on ultrasonography. A computed tomography scan confirmed the presence of a Bosniak type III cystic lesion, which affected the liver and convexity of the right kidney. Surgical intervention involved a right nephrectomy, with removal of the cystic mass. The patient was mobilized on the first postoperative day and was discharged after 7 d. The histological and immunohistochemical examination revealed a low-grade collecting duct renal carcinoma, which is a rare variant of papillary carcinoma, with low malignant potential. The patient did not receive chemotherapy and after 21 mo of follow-up, a radiological examination and laboratory analyses showed normal aspects. No relapse or other complications were reported. CONCLUSION: To manage renal tumors properly, a correct histopathological diagnosis is crucial, as is early diagnosis and correct surgical treatment.

[Application of computed tomography and abdominal pressure measurement in the treatment of giant incisional hernias]. / Számítógépes tomográfia és hasurinyomás-mérés alkalmazása az óriás medián hegsérvek kezelésében.

Introduction: Giant abdominal wall defects represent a major challenge for surgeons. CT scan can determine the ratio between the volume of the hernia sac and the abdominal cavity, determining the extent of the disproportion, which is related to the postoperative abdominal pressure value. Aim: Confirmation of the significance of CT examination in postoperative giant abdominal wall defects, effectiveness analysis of the reconstruction method by abdominal pressure measurement. Method: A prospective study is conducted on patients with giant incisional hernias, with preoperatively performed abdominal CT scan. Tension-free abdominal wall reconstruction is realized with retromuscular Prolene mesh and hernial sac. Abdominal pressure is measured during and after surgery. Patients' follow-up is performed through phone after 2-4-6 months. Results: We present our results through three cases. First case: 48-year-old woman presented a giant recurrent incisional hernia and multiple comorbidities. Maximum defect diameter was: 155 mm, hernia volume: 1536.63 cm3, BMI = 43.6. The patient was discharged after seven days. Second case: 51-year-old male patient presented with multilocular giant incisional hernia, BMI = 26,85. Maximum diameter of the two wall defects were 123 mm and 105 mm, their total volume: 406.41cm3. The patient was discharged after five days. Third case: A 67-year-old male patient presented with giant incisional hernia. The abdominal defect size was 100/100 mm (LL/CC), volume: 258.10 cm3, BMI = 23.7. The patient was discharged after four days. Conclusion: The proper surgical technique can be established based on the preoperative CT scan. Abdominal wall reconstruction with retromuscular Prolene mesh and hernial sac provides a cheap, reliable, tension-free technique. The technique's short-term efficacy can be determined by abdominal pressure measuring through the bladder. Orv Hetil. 2020; 161(9): 347-353.

Immunohistochemical-based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial-mesenchymal transition.

The aim of the present study was to classify colorectal carcinoma (CRC) into molecular subtypes, based on immunohistochemical (IHC) assessments. A total of 112 CRC samples were molecularly classified based on the expression levels of epithelial-mesenchymal transition (EMT)-associated IHC markers. A total of three molecular subtypes were defined: Epithelial, membrane positivity for E-cadherin and ß-catenin, negative for vimentin; mesenchymal, E-cadherin-negative, nuclear ß-catenin- and vimentin-positive; and hybrid cases, epithelial tumor core and mesenchymal tumor buds. Most of the cases were diagnosed as moderately differentiated adenocarcinoma (n=89; 79.46%). The majority of cases (n=100; 89.28%) exhibited a mismatch repair proficient status (microsatellite stable CRCs). A predominance of epithelial-type (n=51; 45.54%) and hybrid CRCs (n=47; 41.96%) was observed, whereas a few cases (n=14; 12.50%) were classified as mesenchymal-type CRCs. This molecular classification was associated with pathological stage (P<0.01), pT stage (P=0.04), pN stage (P<0.01), the grade of tumor budding (P=0.04), and maspin expression in both the tumor core (P=0.04) and the invasion front (P<0.01). The mesenchymal-type cases predominantly exhibited lymph node metastases, high-grade budding and a tendency towards maspin nuclear predominance. All epithelial-type cases with maspin-only expression (n=18) were non-metastatic. Patients with CRC of the epithelial subtype and those with a lymph node ratio (LNR) ≤0.15 presented the best overall survival, followed by those with hybrid and mesenchymal subtypes. Nuclear maspin positivity was more frequent in cases with a high-budding degree compared with those with a low-budding degree (P=0.03). The EMT-associated molecular classification of CRCs may be used to identify the most aggressive CRCs, which show a mesenchymal phenotype, high-budding degree, maspin nuclear positivity and lymph node metastases. The pN stage, LNR and budding degree of patients, which can be evaluated with maspin expression, remain the most important prognostic factors.

Interaction of arylsulfatases A and B with maspin: A possible explanation for dysregulation of tumor cell metabolism and invasive potential of colorectal cancer.

BACKGROUND: Although it has been shown that arylsulfatases are lost in colorectal cancer (CRC) cell lines, their exact role in the carcinogenesis and behavior of this cancer was not elucidated. No data about the correlation between serum and immunohistochemical (IHC) level of arylsulfatases (ARSA, ARSB) in patients with CRC were published yet. AIM: To evaluate the possible prognostic value of ARSA and/or ARSB in CRC, at circulating and protein levels. METHODS: The present study included 45 consecutive patients who were prospectively diagnosed with CRC. For IHC stains (protein expression) ARSA, ARSB and maspin expression were quantified. For these markers, cytoplasmic expression was taken into account. For gene expression study, circulating mRNA was isolated from all patients, before surgery. A group of 45 healthy patients without inflammatory or tumor pathologies was used as control group. Reverse transcription and Taqman Gene Expression Array were used for ARSB gene expression. RESULTS: The preoperative circulating RNA level of the ARSB gene was significantly decreased in patients with CRC (RQ < 1), compared with the control group (RQ > 1). A more significant decrease (RQ < 0.5) occurred in ulcero-infiltrative maspin-positive adenocarcinomas, with a higher degree of tumor budding, diagnosed in locally advanced stages (pT3/4). ARSA/maspin immunopositivity indicated a higher risk for lymph node metastasis, while triple positivity for maspin/ARSA/ARSB and ARSB gene expression level < 0.5 were indicators of CRC aggressive behavior, independent of lymph node status. CONCLUSION: The significant independent negative prognostic factors of CRC are the ulcero-infiltrative aspect, high budding degree, triple positivity for maspin, ARSA and ARSB, and low ARSB gene expression.

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, ß-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane ß-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.

Solid pseudopapillary neoplasm of pancreas: Two case reports.

RATIONALE: About 8384 cases of solid pseudopapillary neoplasms (SPN) of pancreas have been published in English literature, from 1933 to 2018. This is a low-grade tumor that usually occurs in children but is rare in adults and, in exceptional cases, can show extrapancreatic localization. In this paper we present 2 unusual cases of SPNs, 1 with retroperitoneal location (case 1) and 1 that was firstly diagnosed as a G1 neuroendocrine tumor (NET) and showed hepatic metastases after 13 years (case 2). PATIENT CONCERNS: No symptoms in first case. The tumor was incidentally diagnosed, during ultrasound examination. In the second case, the metastasis was observed during regular follow-up. DIAGNOSES: The diagnosis was established based on the histological features and immunohistochemical profile that showed positivity for vimentin, nuclear ß-catenin, cyclin D1, CD10, and SRY-related high-mobility group box 11 and negativity for maspin. INTERVENTIONS: Surgical excision, in both cases. OUTCOMES: No recurrences in first case, at 5 months after diagnosis. Hepatic metastases in the second case, at 13 years after diagnosis, with portal invasion after another 15 months. LESSONS: Without a complex immunoprofile, SPN can be misdiagnosed as NET. SPN can be a low-grade tumor but long-time follow-up is mandatory to detect delayed metastases. A correct diagnosis is necessary for a proper therapeutic management.

Sentinel node biospy using intravital blue dye: An useful technique for identification of skip metastases in gastric cancer.

As the lymph node status remains the main prognostic factor of gastric cancer (GC), several lymph node-based staging systems have been recently proposed for an appropriate postoperative therapy. The identification of sentinel lymph nodes (SLNs) might improve the postoperative protocols. The aim of this study was to present our experience in detecting SLNs in GC using methylene blue dye.We have performed an observational study and retrospectively analyzed all of the consecutive cases of GC operated by the same surgical team and managed by the same pathologists during 2013 to 2015. In all of the cases SLN status was determined using the methylene blue that was intraoperatively administered in the peritumoral subserosal tissue. All blue colored nodes were histopathologically examined. In the node negative cases immunohistochemical stains using AE1/AE3 keratin were performed.The blue SLNs were identified in 48 out of the 50 cases included in the study, with a 96% sensitivity and 87.50% specificity. From the 48 cases, 34 (70.83%) presented positive SLNs; in the other 14 cases the SLNs were negative (29.17%). False negativity was observed in 6 of the 14 cases. In 2 of the cases the false negativity of the group 20 was induced by the anthracotic pigment. In other 2 false negative cases, although no regional metastases were founded, sentinel skip metastases in the group 8 and 15, respectively, were identified.Mapping of the SLNs is a simple and cheap method that might improve the accuracy of LN-based staging of patients with GC and favor identification of skip metastases.

Lymph node ratio, an independent prognostic factor for patients with stage II-III rectal carcinoma.

BACKGROUND: Identification of the proper surgical method and the most reliable prognostic parameters of rectal carcinomas is a challenging issue. The aim of this paper was to determine the possible prognostic role of the number of harvested lymph nodes versus lymph node ratio (LNR) in patients with rectal carcinomas, and the proper value of LNR that can be used as prognostic parameter. MATERIALS AND METHODS: A retrospective study was performed in 186 consecutive patients with rectal carcinomas that underwent surgical resection. The LNR was calculated for cases from stage II-III, and was correlated with classic prognostic parameters and overall survival (OS). RESULTS: A statistically significant difference was found between LNR of 0.15 and OS (p = 0.03), respectively LNR > 0.15 and TNM stage (p < 0.0001), but also tumor infiltration level (p < 0.05). The number of harvested lymph nodes was not correlated with the tumor stage (r = 0.148, p = 0.06) and this parameter did not influence the OS, when the number of 12 or 14 lymph nodes was used as the ideal value (p = 0.6 and p = 0.66, respectively). CONCLUSION: In patients with rectal carcinomas that underwent preoperative chemoradiotherapy, a LNR of 0.15 is a parameter with independent prognostic value, comparing with the number of harvested lymph nodes. The specific LNR should be calculated in larger cohorts.

The epithelial-mesenchymal transition induces aggressivity of mucinous cystic neoplasm of the pancreas with neuroendocrine component: An immunohistochemistry study.

BACKGROUND: Pancreatic mucinous cystic neoplasms (MCN) are rare tumors that are usually diagnosed in females. MATERIALS AND METHODS: In our department, only four of the 109 consecutive cases of pancreatic tumors (3.67%) were diagnosed as MCNs. In this report, we present the characteristics of these four specific cases which also showed unusual HER-2 positivity and neuroendocrine differentiation. RESULTS: The four MCNs were diagnosed in patients with ages between 46 and 75 years. Other clinical particularities were the following: one benign case, splenic rupture as result of a giant cystic tumor on the tail of the pancreas directly invading the spleen in the second one, metastases in the accessory spleen in the third one and invasion of the abdominal vessels in the fourth case. In all of these cases, the ovarian-like stroma tested positivity for calretinin, progesterone receptor (PR) and, in cases 2 and 3, for AE1/AE3 keratin. The malignant tumor cells were marked by carcinoembryonic antigen, HER-2, maspin, PR and the neuroendocrine markers synaptophysin, CD56, and neuron-specific enolase. CONCLUSIONS: These cases highlight the unusually aggressive behavior of pancreatic MCN with invasive carcinomas that share mixed exo- and endocrine components and show epithelial-mesenchymal transition.

Abdominal Compartment Syndrome as a Multidisciplinary Challenge. A Literature Review.

Abdominal Compartment Syndrome (ACS), despite recent advances in medical and surgical care, is a significant cause of mortality. The purpose of this review is to present the main diagnostic and therapeutic aspects from the anesthetical and surgical points of view. Intra-abdominal hypertension may be diagnosed by measuring intra-abdominal pressure and indirectly by imaging and radiological means. Early detection of ACS is a key element in the ACS therapy. Without treatment, more than 90% of cases lead to death and according with the last reports, despite all treatment measures, the mortality rate is reported as being between 25 and 75%. There are conflicting reports as to the importance of a conservative therapy approach, although such an approach is the central to treatment guidelines of the World Society of Abdominal Compartment Syndrome, Decompressive laparotomy, although a backup solution in ACS therapy, reduces mortality by 16-37%. The open abdomen management has several variants, but negative pressure wound therapy represents the gold standard of surgical treatment.

The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.

BACKGROUND: Metastases to the stomach are extremely rare and the metastatic pathway is not well understood. OBJECTIVE: To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells. METHOD: The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents. RESULTS: In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, ß-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma. CONCLUSION: In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/ß-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy.

Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors.

AIM: To evaluate the immunohistochemical (IHC) expression of five biomarkers, commonly involved in epithelial mesenchymal/mesenchymal epithelial transition (EMT/MET), in gastrointestinal stromal tumors (GISTs). METHODS: In 80 consecutive GISTs the IHC examinations were performed using the EMT-related antibodies E-cadherin, N-cadherin, SLUG, V-set and immunoglobulin domain containing 1 (VSIG1) and CD44. RESULTS: The positivity rate was 88.75% for SLUG, 83.75% for VSIG1, 36.25% for CD44 and 10% for N-cadherin. No correlation was noted between the examined markers and clinicopathological parameters. Nuclear positivity for SLUG and VSIG1 was observed in all cases with distant metastasis. The extra-gastrointestinal stromal tumors (e-GISTs) expressed nuclear positivity for VSIG1 and SLUG, with infrequent positivity for N-cadherin and CD44. The low overall survival was mainly dependent on VSIG1 negativity (P = 0.01) and nuclear positivity for SLUG and/or CD44. CONCLUSION: GIST aggressivity may be induced by nuclear up-regulation of SLUG and loss or cytoplasm-to-nuclear translocation of VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The CD44, but not N-cadherin, might also have an independent prognostic value in these tumors. The role of the EMT/MET-related transcription factors in the evolution of GISTs, should be revisited with a larger dataset. This is the first study exploring the IHC pattern of VSIG1 in GISTs.